Regulation of NF-kappaB-dependent lymphocyte activation and development by paracaspase.

Science (New York, N.Y.) ·Vol. 302 ·No. 5650 ·2003-11-28 ·Pages 1581-4

Ruefli-Brasse AA, French DM, Dixit VM

Abstract

Paracaspase (MALT1), a member of an evolutionarily conserved superfamily of caspase-like proteins, has been shown to bind and colocalize with the protein Bcl10 in vitro and, because of this association, has been suggested to be involved in the CARMA1-Bcl10 pathway of antigen-induced nuclear factor kappaB (NF-kappaB) activation. We demonstrate that primary T and B lymphocytes from paracaspase-deficient mice are defective in antigen-receptor-induced NF-kappaB activation, cytokine production, and proliferation. Paracaspase acts downstream of Bcl10 to induce NF-kappaB activation and is required for the normal development of B cells, indicating that paracaspase provides the missing link between Bcl10 and activation of the IkappaB kinase complex.

MeSH Terms

Adaptor Proteins, Signal Transducing Animals Antibody Formation Antigens, CD/analysis B-Cell CLL-Lymphoma 10 Protein B-Lymphocyte Subsets/immunology,physiology B-Lymphocytes/immunology,metabolism,physiology Caspases Cell Differentiation Cell Division Cell Survival Cells, Cultured Cytokines/metabolism Gene Deletion Gene Targeting Guanylate Kinases I-kappa B Kinase Lymphocyte Activation Lymphoma, B-Cell, Marginal Zone/chemistry,metabolism Mice Mice, Inbred C57BL Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein NF-kappa B/metabolism Neoplasm Proteins/chemistry,metabolism Nucleoside-Phosphate Kinase/metabolism Phosphorylation Protein Serine-Threonine Kinases/metabolism Protein Structure, Tertiary Receptors, Antigen, B-Cell/metabolism Receptors, Antigen, T-Cell/metabolism Signal Transduction T-Lymphocyte Subsets/immunology,physiology T-Lymphocytes/immunology,metabolism,physiology Transfection

Chemicals

Adaptor Proteins, Signal Transducing Antigens, CD B-Cell CLL-Lymphoma 10 Protein BCL10 protein, human Bcl10 protein, mouse Cytokines NF-kappa B Neoplasm Proteins Receptors, Antigen, B-Cell Receptors, Antigen, T-Cell Protein Serine-Threonine Kinases Chuk protein, mouse I-kappa B Kinase Ikbkb protein, mouse Ikbke protein, mouse Nucleoside-Phosphate Kinase Guanylate Kinases Caspases Malt1 protein, mouse Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

Ruefli-Brasse Astrid A

Molecular Oncology Department, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.

French Dorothy M

Dixit Vishva M

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

1095-9203

DOI

10.1126/science.1090769

Published

2003-11-28

Epub

2003-00-23

Pages

1581-4

Language

English

Region

United States

NLM ID

0404511

Subset

Corrections

CommentIn

PMID: 14645834

External Links

PubMed source DOI: 10.1126/science.1090769 View journal details

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Regulation of NF-kappaB-dependent lymphocyte activation and development by paracaspase.

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